ABSTRACT Pathological alcohol-seeking behavior is regulated in part by glutamate AMPA receptor (AMPAR) activity in the amygdala. Transmembrane AMPA receptor regulatory proteins (TARPs) profoundly affect the trafficking and function of AMPARs in synaptic and behavioral plasticity. Although the TARP family of proteins is expressed throughout the brain, the TARP ?-8 subtype is restricted to limbic regions including the basolateral amygdala (BLA); a brain region that is critical to addiction. However, the role of TARP ?-8 in alcohol use disorders (AUD) or other addictions is unknown. To fill this gap in knowledge, we propose an innovative set of behavioral, genetic, pharmacological, and molecular studies in mice to evaluate the mechanistic role of TARP ?-8 in escalated self- administration. Elucidating the neural mechanism of this fundamental behavioral pathology has high translational value for understanding the development, progression, and maintenance of AUD. Successful completion of the studies in this application will provide fundamental mechanistic insights into TARP ?-8 regulation of pathological alcohol-seeking behavior. Moreover, this work moves the field forward in understanding the molecular mechanisms by which alcohol hijacks reward processes and has potential to inform development of new pharmacotherapeutic strategies that target AMPAR function in a highly selective brain region-specific manner.